Posttraumatic stress disorder (PTSD) is a chronic and distressing condition, with significant morbidity, and possibly increased mortality, affecting up to 9% of the U.S. population, or 15% if subclinical cases are included. Rape Is one of the most common traumata, affecting over 25% of the female population and giving rise to PTSD in 70-90% of victims. Among veterans of combat in Vietnam, 26-30% developed chronic PTSD. Recent studies have indicated that anti-depressant drugs are superior to placebo (PBO) in veterans with PTSD, and open trials have shown efficacy for fluoxetine (FLU) in both veterans and non-veterans. No studies to date have evaluated pharmacotherapy in rape victims with chronic PTSD. In this proposal, we aim to (a) evaluate the effectiveness of 12 weeks' treatment with FLU against PBO in chronic PTSD secondary to rape and combat trauma; (b) evaluate the effects of 9 months' double-blind discontinuation therapy In FLU responders; (c) compare the response to treatment across the two patient populations, i.e. female rape victims and male combat veterans; (d) examine predictors of response. Sixty rape trauma patients and sixty combat veterans will separately be assigned to receive double-blind treatment with FLU or PBO for 12 weeks, followed by a 9 month double-blind extension phase, in which FLU responders will be re-randomized 6 months after baseline to FLU or PBO, in order to evaluate differing durations of continuation therapy. PBO responders at week 12 will continue on PBO double-blind throughout, in order to evaluate duration of response. Outcome will be assessed by Independent Evaluator ratings and self-report scales before, during and after treatment. Scales will include the SCID, Structured Interview for PTSD, Impact of Event Scale, Hamilton scales, Global Evaluations, disability scales and personality measures (SCID-II and Eysenck). Long range goals and implications of the study are to establish the role of an antidepressant in short and long term treatment of one of the country's most common, yet largely preventable, chronic psychiatric disorders, and to compare treatment response to FLU and PBO in two different populations (male combat veterans and female rape trauma victims) with a common diagnosis.